fig1

Figure 1. M1 macrophage metabolism. M1 macrophage metabolism is characterized by enhanced glycolysis and increased flux through the pentose phosphate pathway (PPP) to produce NADPH, which is used to produce the inflammatory mediators nitric oxide (NO) and reactive oxygen species (ROS). In M1 macrophages, the tricarboxylic acid (TCA) cycle is truncated, which leads to the accumulation of succinate and citrate metabolites. Succinate accumulation leads to stabilization of hypoxia-inducible factor 1 alpha (HIF-1α) and transcription of pro-inflammatory and glycolytic genes, whereas citrate is used for synthesis of fatty acids. ACLY: ATP-citrate lyase; α-KG: α-ketoglutarate; FAS: fatty acid synthase; GLUT: glucose transporter; iNOS: inducible nitric oxide synthase; LDH: lactate dehydrogenase; MCT: monocarboxylate transporter; SLC: solute carrier.